Ro52/TRIM21 – From host defense to autoimmunity

Holwek, Emilia; Opinc-Rosiak, Aleksandra; Sarnik, Joanna; Makowska, Joanna

doi:10.1016/j.cellimm.2023.104776

Cited by 1 publication

(1 citation statement)

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“…We found that the coiled-coil and the PRYSPRY domains of TRIM21 are important for its interaction with FAT10. This is in line with other studies which showed that the PRYSPRY domain of TRIM21 is involved in protein-protein interactions ( van Gent et al, 2018 ; Holwek et al, 2023 ). Similarly, the coiled-coil domain of TRIM21 is important for the formation of a catalytically active homodimer of TRIM21 ( van Gent et al, 2018 ).…”

Section: Discussionsupporting

confidence: 93%

FAT10 inhibits TRIM21 to down-regulate antiviral type-I interferon secretion

Saxena,

Inholz,

Basler

et al. 2024

Life Sci. Alliance

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The ubiquitin-like modifier FAT10 is upregulated under pro-inflammatory conditions, targets its substrates for proteasomal degradation and functions as a negative regulator of the type-I IFN response. Influenza A virus infection upregulates the production of type-I IFN and the expression of the E3 ligase TRIM21, which regulates type-I IFN production in a positive feedback manner. In this study, we show that FAT10 becomes covalently conjugated to TRIM21 and that this targets TRIM21 for proteasomal degradation. We further show that the coiled-coil and PRYSPRY domains of TRIM21 and the C-terminal diglycine motif of FAT10 are important for the TRIM21-FAT10 interaction. Moreover, upon influenza A virus infection and in the presence of FAT10 the total ubiquitination of TRIM21 is reduced and our data reveal that the FAT10-mediated degradation of TRIM21 diminishes IFNβ production. Overall, this study provides strong evidence that FAT10 down-regulates the antiviral type-I IFN production by modulating additional molecules of the RIG-I signaling pathway besides the already published OTUB1. In addition, we elucidate a novel mechanism of FAT10-mediated proteasomal degradation of TRIM21 that regulates its stability.

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Section: Discussionsupporting

confidence: 93%